Ophthalmic Compositions

ABSTRACT

The present invention relates to compositions providing improved substantivity, comfort and/or feel to the eye upon application. The present invention further relates to compositions comprising a cellulose derivative in combination with tamarind seed extract and hyaluronic acid in ratios that mimic the physical properties of human tears on the eye.

RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser. No. 16/113,073, filed Aug. 27, 2018, which claims thebenefit of the earlier filing date of U.S. Provisional PatentApplication No. 62/552,066, filed Aug. 30, 2017, the entirety of whichapplication is hereby incorporated by reference herein as if fully setforth herein.

FIELD OF THE INVENTION

The present invention relates to compositions providing improvedsubstantivity, comfort and/or feel to the eye upon application. Thepresent invention further relates to compositions comprising a cellulosederivative in combination with tamarind seed extract and hyaluronic acidin ratios that mimic the physical properties of human tears on the eye.

BACKGROUND OF THE INVENTION

Ophthalmic solutions are sterile solutions, free or substantially freefrom foreign particles and/or microorganisms, for instillation into theeye. For certain applications, ophthalmic solutions do not containmedications and are used as lubricating, tear-replacing, and eye washsolutions, and/or packing solutions, multipurpose, and other solutionsfor contact lenses. Ophthalmic solutions can also containpharmacologically active ingredients and be used to treat suchenvironment related eye conditions as dry eye, allergies, eye infectionssuch as pink eye, minor eye irritations or conjunctivitis, orstructurally related eye conditions such as glaucoma. They can also beused diagnostically by opticians as mydriatic compositions to dilate thepupils of patients during eye examinations.

To avoid or reduce such negative effects of ophthalmic compositions onthe eye such as the feel of “dragging” (of such compositions) across theeye upon blinking, blurriness upon application to the eye and discomfort(of such compositions) due to unpleasant film formation of the eye, itis critical to provide ophthalmic compositions which mimic (i.e.,physical properties which are the same as or similar to) the physicalproperties of tears on the eye.

There is, therefore, a need for compositions useful as ophthalmicsolutions, which upon application to the eye, provide improved eye feelby exhibiting the same or similar physical properties as human tearswith respect to the surfaces of the eye and eye lid. This compositionwill aid in increased tear stability, a reduction in moisture loss fromthe tears, and protection of the ocular surface

SUMMARY OF THE INVENTION

The present invention relates to a composition, comprising:

-   -   a polymer mixture comprising        -   i. a cellulose derivative;        -   ii a tamarind seed extract; and        -   iii hyaluronic acid;    -   optionally, an oil component;    -   optionally, a surfactant; and    -   optionally, an aqueous component        wherein the cellulose derivative, tamarind seed extract and        hyaluronic acid are combined at a ratio of: 1 to 10 parts        cellulose derivative:1 to 4 parts tamarind seed extract:1 to 2        parts hyaluronic acid, to form the polymer mixture.

DETAILED DESCRIPTION OF THE INVENTION

The compositions and methods of the present invention can comprise,consist of, or consist essentially of the steps, essential elements andlimitations of the invention described herein, as well any of theadditional or optional ingredients, components, or limitations describedherein. The term “comprising” (and its grammatical variations) as usedherein is used in the inclusive sense of “having” or “including” and notin the exclusive sense of “consisting only of.” The terms “a” and “the”as used herein are understood to encompass the plural as well as thesingular.

Unless otherwise indicated, all documents cited are, in relevant part,incorporated herein by reference; the citation of any document is not tobe construed as an admission that it is prior art with response to thepresent invention. Furthermore, all documents incorporated herein byreference or incorporated herein by reference in their entirety are onlyincorporated herein to the extent that they are not inconsistent withthis specification.

In certain embodiments, the present invention as disclosed herein may bepracticed in the absence of any compound or element (or group ofcompounds or elements) which is not specifically disclosed herein.

Cellulose Derivatives

The compositions of the present invention comprise a cellulosederivative. Suitable cellulose derivatives include, but are not limitedto, hydroxyalkyl cellulose polymers and alkyl hydroxyalkyl cellulosepolymers such as hydroxyethyl cellulose, hydroxypropyl cellulose, cetylhydroxyethyl cellulose and mixtures thereof; methyl cellulose; methylcellulose derivatives such as carboxymethyl cellulose (crosscarmellose),hydroxymethylcellulose, hydroxymethylcellulose and mixtures thereof;hydroxymethycellulose derivatives such as hydroxypropyl methylcellulose(HPMC or hypromellose) and hydroxybutyl methyl cellulose and mixturesthereof; and mixtures of any of the above cellulose derivatives, Incertain embodiments the cellulose derivative is hydroxypropylmethylcellulose.

In certain embodiments, the cellulose derivative used herein is a lowviscosity grade cellulose derivative. By the term “low viscosity grade”is meant a cellulose derivative having a viscosity of from about 1-100cps (at 2% aqueous at 20° C.). Such low viscosity grades are indicatedby notations like “E3” as in the case of Hypromellose E3 2910 orHypromellose E3 Premium 2910, which compounds typically have a viscosityof from about 1-10 cps (at 2% aqueous at 20° C.). A low viscosity gradeof carboxmethylcellulose (CMC) is typically indicated by notations like“L”, as in the case of Sodium CMC 7L2P, which compounds typically have aviscosity of from about 25-50 cps (at 2% aqueous at 20° C.).

The cellulose derivative can be present in the composition of thepresent invention at concentrations of from about 0.1% w/v to about 2.5%w/v, optionally from about 0.2% w/v to about 1.0% w/v, or optionallyfrom about 0.2% w/v to about 0.5% w/v of the total composition.

Tamarind Seed Extract

The compositions of the present invention also comprise a tamarind seedextract. Tamarind tree is widespread in India, Africa and in the SouthEast Asia. In Middle Eastern countries, tamarind juice from the tamarindfruit can be a drink prepared by infusing dried tamarind pulp. Tamarindcan also be useful for the preservation of food products and as a saucein recipes.

The tamarind seed finds various applications, once ground to the powderform (known as “tamarind gum” or “tamarind kernel powder”). Commerciallyavailable tamarind kernel powder can be employed as thickener and asizing agent in textile and paper industries; and as thickening,gelling, stabilizing and binding agent in food and pharmaceuticalindustries.

General properties, chemical composition and chemical structure oftamarind kernel powder and of tamarind seed polysaccharide can be foundin: Gupta V, Puri R, Gupta S, Jain S, Rao G K.; Tamarind kernel gum: anupcoming natural polysaccharide. Syst Rev Pharm; 2010; 1:50-4.

Tamarind seed polysaccharide or extract (TSP) is a nonionic, neutral,branched polysaccharide comprising a cellulose-like backbone substitutedby xylose (a 1→6) and galacto (β1→2)xylose (a 1→6) substituents (Lang P.et al., Macro molecules, 1993, 26, 3992-3998).

As is known by those skilled in the art, the tamarind seedpolysaccharide is extracted from tamarind seeds has been described as aviscosity enhancer showing mucomimetic, mucoadhesive, and bioadhesiveactivities. Several features make TSP an attractive candidate as avehicle for ophthalmic medicaments, since it (i) is completely devoid ofocular toxicity; (ii) is on the market as a tear fluid substitutebecause of its activity in preventing alterations of the corneal surfaceknown as keratoconjunctivitis sicca; and (iii) increases thecorneal-wound healing rate when used in concentrations between 0.25% and1%.

The tamarind seed extract can be present in the composition of thepresent invention at concentrations of from about 0.05% w/v to about 2%w/v, optionally from about 0.1% w/v to about 1% w/v, or optionally fromabout 0.2% w/v to about 0.5% w/v of the total composition.

Hyaluronic Acid

Hyaluronic acid is used in literature to designate an acidicpolysaccharide with various molecular weights constituted by residues ofD-glucuronic acid and N-acetyl-D-glucosamine, which naturally occur incellular surfaces, in the basic extracellular substances of theconnective tissues of vertebrates, in the synovial fluid of joints, inthe vitreous humor of the eye, in the tissue of the human umbilical cordand in cocks' combs.

As a therapeutic agent, hyaluronic acid and its salts have been usedespecially in therapy for arthropathies, such as in veterinary medicinefor the cure of arthritis in horses [Acta Vet. Scand. 167, 379 (1976)].As an auxiliary and substitutional therapeutic agent for natural tissuesand organs, hyaluronic acid and its molecular fractions and their saltshave been used in ophthalmic surgery (see for example Balazs et al.,Modern Problems in Ophthalmology, Vol. 10, 1970, p. 3—E. B. Strieff, S.Karger eds., Basel; Viscosurgery and the Use of Sodium HyaluronateDuring Intraocular Lens Implantation, Paper presented at theInternational Congress and First Film Festival on IntraocularImplantation, Cannes, 1979; U.S. Pat. No. 4,328,803 with a summary ofthe literature on the uses of HY in ophthalmology; and U.S. Pat. No.4,141,973.

In certain embodiments, the HA has a molecular weight between about500,000 daltons and about 4,000,000 daltons, or, optionally, betweenabout 1,000,000 daltons and about 2,000,000 daltons, or, optionally,between about 1,200,000 daltons and about 1,800,000 daltons. Certainembodiments of the present invention contain between about 0.1% andabout 0.5% HA, or, optionally, between about 0.2% and about 0.4% HA, or,optionally, about 0.2% HA. More detailed discussions of HA can be foundin U.S. Patent Publication 20060094643; and U.S. Pat. Nos. 3,396,081;3,862,003; 4,141,973; 4,517,296; 4,851,521; 4,965,353; 5,202,431;5,316,926; 6,090,596; and 6,339,074, each of which patents are hereinincorporated by reference in its entirety.

The hyaluronic acid can be present in the composition of the presentinvention at concentrations of from about 0.05% w/v to about 1% w/v,optionally from about 0.075% w/v to about 0.5% w/v, or optionally fromabout 0.1% w/v to about 0.4% w/v of the total composition.

In one embodiment, the cellulose derivative is combined with tamarindseed extract and hyaluronic acid to form a polymer mixture for use inimproving the physical properties of ophthalmic compositions to mimicthe physical properties of tears, namely so as to improve such physicalproperties of the ophthalmic composition as: surface tension, moistureretention, shear thinning, elastic modulus and phase angle.

Surface Tension Property

The typical volume of a single drop of an ophthalmic composition (about40-50 microliters) generally exceeds the total tear volume that is onthe ocular surface prior to application. This surge in volume producedby an eye drop may exceed the tear “holding capacity” of an eyeresulting in an excess of composition which spills over the lid or exitsat the nasal or temporal canthi. Human tear fluid as secreted has asurface tension of about 40 dynes/cm which is lower than water (about 70dynes/cm), making the tear fluid able to wet the ocular surfaceeffectively. In addition, this low surface tension allows tears to wetthe periocular skin effectively which leads to visible drainage of thetears, or tearing, away from the ocular surface onto the skin.

In certain embodiments, the cellulose derivative, tamarind seed extractand hyaluronic acid polymer mixture is incorporated such that thesurface tension of the composition ranges from about 40.8 dynes/cm to51.9 dynes/cm, optionally from about 42 dynes/cm to about 48 dynes/cm,or optionally from about 44 dynes/cm to about 46 dynes/cm. The surfacetension can be measured by utilizing the pendant drop method of aRame-Hart contact angle goniometer (Model 100-00 Series) and amicro-syringe (with a 22 gauge needle) and with DROPimage Advancedsoftware (ver. 2.7) as each is supplied by Rame-Hart Instrument Co.,Netcong, N.J. The DROPimage Advanced software captures and analyzes thedrop dimensions and profile characteristics in order to accuratelycalculate the surface tension of a liquid utilizing a built-incalculation based on the Young La-Place equation.

The Rame-Hart—DROPimage Advanced Software Pendant Drop Method

Test Equipment:

-   -   Rame-Hart Model 100-00 Series Contact Angle Goniometer    -   Stocker and Yale Image Lite (model number 20, supplied by        Stocker and Yale, Inc.)    -   Rame-Hart Imaging System U1 Series Video Camera    -   DROPimage Advanced 2.7 Software    -   Microsyringe with 22 gauge needle (supplied by Gilmont)

Procedure:

The procedural steps of the Rame-Hart—DROPimage Advanced softwarePendant Drop Method are as follows (for performance in a mannerconsistent with protocol provided with Rame-Hart goniometer andDROPimage software):

-   -   a.) the test samples are drawn into the provided micro-syringes        having the needles;    -   b.) the Dropimage software is accessed and program opened (to        display live video captured by the goniometer's digital video        camera); the image light is switched to the “on” position; and        the video camera is focused to ensure needle of syringe        containing sample can be seen at top of live video;    -   c.) from the software programs file menu, an experiment is        selected for performance using the “Surface Tension-Pendant        Drop”;    -   d.) Phase Data for the Experiment is entered:        -   i. Droplet Phase input: Water;        -   ii. External Phase input: Air, and        -   iii. Solid Phase: Steel;    -   e.) Experiment Timing Data is entered: Total Number of        Measurements: 10; Time Interval for each measurement: 1 second;    -   f.) a pendant drop of the test sample is hung from needle of the        micro-syringe by slowly turning barrel of the micro-syringe        clockwise;    -   g.) the Stocker and Yale Image Lite is used to improve drop        clarity and focus (measurements should be performed in dark room        with minimal vibrations);    -   h.) when drop clarity and focus has been achieved (i.e., the        outline of the drop is dark and crisp), the software program is        signaled to run the experiment;    -   i.) a picture will be taken of the drop and will appear to the        left of the screen;    -   j.) the cross-hairs over laying the picture are moved to capture        the entire drop from its top shoulders without including needle        and the software program is signaled to to take measurements and        a picture of the drop hanging from the needle at 0.1 second        intervals from 0 to 1 second as the video camera rolls for 1        second;    -   k.) a report will be generated, indicating the “Gamma” (i.e.,        surface tension) of the drop; the mean “Gamma” and the standard        deviation of the measurement.

Moisture Retention Property

Moisture retention rate refers to the rate at which moisture is lostfrom a composition over time, at a given temperature and relativehumidity (RH), after application the composition to the eye as measuredby the Dynamic Vapor Sorption (DVS) Intrinsic-1 serial number P14F0068equipped with DVS-Intrinsic Control Software (ver. 1.0.5.1). DVSIntrinsic Control software utilizes proprietary technology to preciselyweigh the mass of a fixed quantity of a composition while strictlycontrolling steps of time, start and finish relative humidity, and startand finish temperature as selected. Although the system is typicallyused for sorption and desorption curves by inserting isotherm steps atincreasing or decreasing humidity, the system is used for purposes ofthis application to compare water loss of compositions by subjectingeach composition to a fixed temperature and relative humidity for aperiod of time and comparing weight or water loss.

In certain embodiments, the cellulose derivative, tamarind seed extractand hyaluronic acid polymer mixture is incorporated such that the rateof moisture loss for the composition is less than 1 mg/3 minutes at 37°C. and 70% relative humidity.

The DVS Intrinsic Measurement System and DVS-Intrinsic Control SoftwareMethod

Test Equipment:

-   -   Dynamic Vapor Sorption Intrinsic-1 serial number P14F0068        instrument supplied by Dynamic Vapor Sorption Measuring Systems,        LTD    -   CO₂ gas source    -   DVS Intrinsic Control Software version 1.0.5.1, including the        SMS DVS Std Macros add-on program, supplied by Dynamic Vapor        Sorption Measuring Systems, LTD    -   Loading pans for DVS Intrinsic-1 serial number P14F0068    -   Mettler Toledo Analytical balance (Model XS205DU, supplied by        Mettler Toledo)

Procedure:

The procedural steps of the DVS Intrinsic Measurement System andDVS-Intrinsic Control Software Method are as follows (for performance ina manner consistent with any protocol information provided with the DVSIntrinsic Measurement System and DVS-Intrinsic Control Software System):

-   -   a.) the DVS-Intrinsic Control Software is accessed and program        opened;    -   b.) from the software program's file menu, an experiment method        is created using the “Insert Isotherm Steps” method;    -   c.) the following parameters are entered:        -   i. a single input time of 800 minutes,        -   ii. start humidity of 70% RH,        -   iii. stop humidity of 70% RH,        -   iv. start temperature of 37° C., and        -   v. stop temperature of 37° C.;    -   d.) the software program is signaled to store the method;    -   e.) the method is then loaded, and the target temperature of        37° C. and 70% RH is verified using the “Instrument Data” tab        displayed by the software program.    -   f.) test sample data is loaded in the software program;    -   g.) tare balance a clean weighing pan by placing the pan on the        guide wires in the system chamber using tweezers and close the        chamber tightly;    -   h.) allow time for the instrument to equilibrate at 37° C. and        70% RH;    -   i.) once the pan is tared, three green lights will appear        indicating completion of tare process.    -   j.) the software program is immediately signaled to finish tare        process, open the chamber and quickly remove the loading pan        from its position hanging on the guide wires;    -   k.) immediately weigh 140 mg of test sample in the tared pan;    -   l.) place the pan containing test sample back into the chamber        and close chamber tightly;    -   m.) when the software program displays the mass reading of 140        mg, the software program is signaled to run the method;    -   n.) once the method is run on all desired test samples, the data        is analyzed and compared by a macro add-in program called SMS        DVS Std Macros. The DVS Analysis Suite runs from within        Microsoft Excel to provide an environment for plotting the data        with the export data function exporting the DVS data into an        excel spreadsheet.

Shear Thinning Property

Shear thinning describes the property of non-Newtonian fluids which havedecreased viscosity when subjected to shear strain. As used herein, the“shear-thinning” property of the compositions of the present inventionrefers to the rheologic property of the compositions such that thecompositions upon application of a shear stress (e.g., from pumping,dropping or pouring, dispensing, during manufacture ordistribution/application, of the compositions) changes viscosity andbecomes less thick and flows more like water. In certain embodiments,the cellulose derivative, tamarind seed extract and hyaluronic acid areincorporated such that compositions of the present invention have aviscosity of from about 30 to 100, optionally from about 50 to 80centipoise (cps) at zero shear (or rest) are capable of being instilledand remain substantive to the eye. In certain embodiments, the cellulosederivative, tamarind seed extract and hyaluronic acid polymer mixture isincorporated such that the compositions have a viscosity of less than 30cps at the shear rate of blinking ( 1/100 sec.); such lower viscosityupon blinking prevents or reduces the dragging feeling of a thick drop(i.e., drop with viscosity of 30 to 100 cps as mentioned above) betweenthe eye and eyelid. The polymer mixture would be preferred to have amarked shear thinning such that the viscosity at rest of 30 to 100 cpsideally decreases to the viscosity of tears (4.4 to 8.3 cps) at theshear rate of blinking ( 1/100 sec.).

To determine directional differences with respect to the extent of shearthinning of polymer compositions at rest (i.e., zero shear) vs. at theshear rate of blinking (i.e. 1/100 sec.), the TA Instruments AR2000rheometer can be used to test flow, creep, and oscillation modes. Usingthe step ramp flow mode of the rheometer, flow behavior over a varietyof shear stress and shear rates can be determined by selecting shearrate ranges at a constant temperature. Resulting flow curves can becompared to determine viscosity as a function of shear rate for variouscompositions. The greater the rate of viscosity drop would indicatematerial that is more shear thinning (i.e., pseudoplastic) behavior.

AR2000 Flow Test Method:

Test Equipment:

-   -   AR2000 rheometer (supplied by TA Instruments)    -   Thermo Cube Solid State Cooling System (model number        10-300-ICL-IFN-HT-CT    -   Steel 4 cm flat plate (40 mm) Cone and Plate Geometry, serial        number 951103

Procedure:

The procedural steps of the AR2000 Flow Test Method are as follows (forperformance in a manner consistent with any protocol informationprovided with AR2000 rheometer:

-   -   a) the rheometer and cooling system are both switched “on”;    -   b) the barrier shield from the drive shaft of the rheometer is        removed;    -   c) the “TA Rheological Advantage” icon displayed by the software        program is selected;    -   d) the geometry is screwed onto the drive shaft of the        rheometer;    -   e) the geometry tab is selected from toolbar displayed by the        software program and from the dropdown menu “40 mm steel plate        geometry (951193)” is chosen as the geometry;    -   f) Once the geometry is chosen, “map geometry” is displayed by        the software program and the rheometer is allow time to map the        geometry.    -   g) the instrument tab at the top tool bar as displayed by the        software program is selected and “zero gap” tab is selected to        zero the gap for this geometry selected in step e) and the        geometry is brought closer to the bottom Peltier plate of the        AR2000 without letting it touch the plate using the up and down        arrows by displayed by the software program.    -   h) once gap is zeroed, and the geometry is allowed to rise to        40,000 um in preparation for loading test sample (by selecting        the “back off” tab displayed by the software program).    -   i) the test sample is loaded such that it covers the entire area        below the circumference of the geometry; (Excess air bubbles        should be removed from the test sample.)    -   j) “Instrument Status” icon displayed by the software program is        selected and

“Gap” icon displayed by the software program is, then, selected and thegap is adjusted to 1000 um.

-   -   k) the “send” icon displayed by the software program is then        selected to lower the geometry onto the test sample.    -   l) a conditioning step of one minute, 25° C. is entered, with no        pre-shear and, for the flow step, a Ramp type of steady state        flow with a start controlled variable of 0 sec⁻¹ to an end        variable of 200 sec⁻¹ is entered;    -   m) the experiment is started and the generated data retrieved        using the AR2000 Data Analysis program, which transfers the        generated viscosity at “blinking” and viscosity “at rest” (i.e.,        zero shear) data to an Excel program (spreadsheet generator) for        comparisons.

A composition can also be characterized by three parameters, elasticmodulus G′, the viscous modulus G″, and its phase angle δ. G′ indicatesthe elasticity of the composition subjected to strain (i.e., itsresilience to deformation before it yields). Thus, an elasticcomposition will be able to absorb the applied energy for a greaterrange of shear stresses before it breaks down. This is typicallyindicated by a nearly horizontal G′ when plotted as an amplitude sweepcurve. The breakdown of thickening matrix is indicated by the point atwhich G′ drops. The shear stress at which this happens is the criticalshear stress, and the lower the number, the less resilient thecomposition. Similarly, the G″ is a measure of the viscous nature of thecomposition, i.e., how much it will flow as a consequence of the appliedshear. Some compositions are stiff and resist flow until they breakdown. Others flow at all shears. High G′ and Low G″ implies a stiffthick gel, while low G′ and high G″ implies a runny, highly flowablecomposition.

The ratio between G′ and G″ is 6, and gives a measure of the relative“solid” to “fluid” nature of the composition. Phase angles near zeroimply a nearly solid-like behavior while those near 90° imply aliquid-like behavior.

In certain embodiments, the cellulose derivative, tamarind seed extractand hyaluronic acid are incorporated to form viscoelastic compositionshaving:

-   -   i. an elastic modulus G′ greater than 0.70 (or about 0.70)        Pascals, optionally from about 0.70 (or about 0.70) to about        0.80 (or about 0.80), optionally 0.73 (or about 0.73) to 0.78        (or about 0.78) Pascals, at a strain of from 0 to 0.85; and    -   ii. a phase angle δ of from about 40° to about 65°, or        optionally from about 50° to about 60°        so as to provide a composition having less fluidity, less        deformation, and greater retention in the eye.

The parameters of elastic modulus G′, and its phase angle δ can bemeasured by performing an amplitude sweep of a strain of 0.1 to 10 usingthe oscillation testing mode of a Bohlin CVOR rheometer and a 60 mmacrylic parallel plate geometry.

Bohlin CVOR Rheometer Visco-Elastic Property Test Method:

Test Equipment:

-   -   Bohlin rheometer (Model number C-VOR-150-900; supplied by        Malvern Instruments, Inc.)    -   Neslab Water Bath, Model 100-00    -   Acrylic 60 mm parallel plate geometry

Procedure:

The procedural steps of the Bohlin CVOR Rheometer Visco-Elastic PropertyTest Method are as follows (for performance in a manner consistent withany protocol information provided with the Bohlin CVOR Rheometer TestMethod):

-   -   a) the rheometer and water bath are both switched “on”;    -   b) the lock from the drive shaft of the rheometer is unlocked;    -   c) the “Bohlin rheometer” icon, oscillation mode, and amplitude        sweep are each sequentially selected as they are displayed by        the software program;    -   d) the geometry (i.e., the acrylic 60 mm parallel plate) is        screwed onto the drive shaft of the rheometer;    -   e) a zero gap is selected to ensure that the correct geometry is        displayed by the software program. Once the rheometer signals        that the gap is zeroed, select the upward arrow displayed by the        software program to raise the gap high enough to load the test        sample.    -   f) the test sample is loaded onto the Peltier plate of the        rheometer such that it covers the entire area below the        circumference of the geometry; (Excess air bubbles should be        removed from the test sample.)    -   g) Select the “Diagram of Experiment” icon displayed by the        software program, and then select a “Ramp of Strain” from 0.01        to 10.    -   h) the experiment is started, generating an amplitude sweep and        an accompanying table of data as the experiment progresses to        completion;    -   i) From the curves, the linear viscoelastic regions can be        identified and compared. At a stain of 0.85, and the        corresponding elastic modulus, G′ and phase angle δ are recorded        for each of the test samples.

In certain embodiments, the compositions of the present inventionexhibit the above rheologic properties when the cellulose derivativesare combined with the tamarind seed extract and hyaluronic acid at aratio of: 1 to 10, optionally 1 to 5, or optionally 1.5 to 3 partscellulose derivative: 1 to 4 parts tamarind seed extract:1 to 2 partshyaluronic acid, to form the polymer mixture; and, in certainembodiments, where the total concentration of the polymer mixture ofcellulose derivative, tamarind seed extract and hyaluronic acid isgreater than 0.4% (or about 0.4%) to 0.9% (or about 0.9%), optionallyfrom 0.45% (or about 0.45%) to 0.55% (or about 0.55%), by weight, of thetotal composition of the present invention. In certain embodiments, thecellulose derivative is hydroxypropylmethyl cellulose.

In certain embodiments, the total concentration of any non-ionic and/oranionic polymers of the composition is from (or greater than) 0.4% (orabout 0.4%) to about 1.0% (or about 1.0%), by weight, of the totalcomposition of the present invention.

Optional Components Polyquaternium Compound

In certain embodiments, the compositions of the present inventioncomprise a polyquaternium compound. Polyquaternium is the InternationalNomenclature for Cosmetic Ingredients designation for severalpolycationic polymers that are used in the personal care industry. Thesepolymers have quaternary ammonium centers in the polymer. INCI hasapproved at least 37 different polymers under the polyquaterniumdesignation. They are cationic molecules. Some have antimicrobialproperties, and find particular application in conditioners, shampoo,hair mousse, hair spray, hair dye, contact lens packing solution andcontact lens solutions (including eye lubricants, rewetting solutions,rinsing solutions etc.). Different polymers are distinguished by thenumerical value that follows the word “polyquaternium”. The numbers areassigned in the order in which they are registered rather than becauseof their chemical structure. Some of the more common quaternary ammoniumcompounds include those generically referred to in the art aspolyquaternium.

In some embodiments, the composition will contain one or more of apolyquaternium compound(s) having a weight average molecular weight offrom about 150 to about 15,000 Daltons, optionally from about 200 toabout 13,500 Daltons, or optionally from about 250 to about 12,000Daltons at a level of from about 0.0005% w/v to about 0.1000% w/v, orfrom about 0.0010% w/v to about 0.0200% w/v, or from about 0.0010% w/vto about 0.0050% w/v of the total composition.

Examples of suitable polyquaternium compounds include, but are notlimited to, polyquatemium-1, polyquaternium-10, polyquaternium-42 ormixtures. In an embodiment of the present invention, the polyquaterniumcompound is polyquaternium-42.

Polyquatemium-1 is also known as ethanol, 2,2′,2″-nitrilotris-, polymerwith 1,4-dichloro-2-butene andN,N,N′,N′-tetramethyl-2-butene-1,4-diamine. Polyquatemium-10 is alsoknown as quaternized hydroxyethyl cellulose. Polyquatemium-42 is alsoknown as poly[oxyethylene(dimethylimino)ethylene (dimethylimino)ethylenedichloride].

Borate

In certain embodiments, the compositions of the present inventioncomprise a borate. As used herein, the term “borate” shall refer toboric acid, salts of boric acid and other pharmaceutically acceptableborates, or combinations thereof. Suitable borates include, but are notlimited to, boric acid; alkaline metal salts such as sodium borate,potassium borate; alkaline earth metal salts such as calcium borate,magnesium borate; transition metal salts such as manganese borate; andmixtures thereof.

The borate compound can be present in the composition of the presentinvention at concentrations of from about 0.004% w/v to about 1.5% w/v,optionally from about 0.01% w/v to about 1.2% w/v, or optionally fromabout 0.06% w/v to about 1.0% w/v of the total composition.

Antimicrobial Mixture

In certain embodiments, the compositions of the present inventioncomprise an antimicrobial mixture comprising one or more nutrient(s)and, optionally, one or more electrolyte(s).

Nutrients useful in the antimicrobial mixture of the present inventioninclude, but are not limited to, lactate salts (such as sodium lactateor potassium lactate), phosphate salts (such as sodium phosphate,disodium phosphate and potassium phosphate), monosaccharides (such asglucose, fructose or galactose), disaccharides, citrates (such as citricacid, sodium citrate, potassium citrate) and mixtures thereof.

In certain embodiments, the nutrients include (are selected from orselected from the group consisting of) lactate, glucose and mixturesthereof. The present inventors have observed that glucose provides asignificant contribution to the antifungal activity of the antimicrobialmixtures. The lactate follows the glucose with regard to thesignificance of its contribution to the antifungal activity of theantimicrobial mixture. And, in certain embodiments, when combined withthe glucose, the lactate/glucose combination provides an even higherdegree of the antifungal activity than glucose alone.

While it was observed that citrate, ascorbic acid or glycine,individually, contribute minimally to the antifungal activity of theantimicrobial mixture, it was found that the combination of citrate,lactate and glycine was observed to improve the antifungal contributionof each of the glucose or lactate to the antimicrobial mixture, with thelargest improvement observed when the glucose and lactate are combinedwith citrate, ascorbic acid and glycine.

In certain embodiments, the antimicrobial mixture further compriseselectrolytes useful in the antimicrobial mixture of the presentinvention include, but are not limited to, alkaline earth metal salts,such as alkaline earth metal inorganic salts, and mixtures thereof.Suitable examples include potassium salts such as potassium chloride andpotassium phosphate), magnesium salts (such as magnesium chloride),sodium salts (such as sodium chloride); counter anions such as chlorideand mixtures thereof.

In certain embodiments, the nutrient(s) and electrolyte(s) are presentin the antimicrobial mixture such that when incorporated to form thecompositions of the present invention: i) the total nutrientconcentration, in the total composition of the present invention, isfrom about 1.0 mMol/L to about 4.0 mMol/L, optionally from about 2.0mMol/L to about 3.0 mMol/L, or optionally from about 2.8 mMol/L to about3.0 mMol/L of the composition; and, when incorporated, ii) the totalelectrolyte concentration, in the total composition of the presentinvention, is from about 20 mMol/L to about 80.0 mMol/L, optionally fromabout 30 mMol/L to about 70 mMol/L, or optionally from about 40 mMol/Lto about 60 mMol/L of the composition

In certain embodiments, one or more, optionally two or more, optionallythree of more, optionally four or more of the nutrients and, optionally,one or more, optionally two or more, optionally three of more,optionally four or more of the electrolytes are present in theantimicrobial mixture such that:

A. the total nutrient concentration in the composition of the presentinvention comprises the individual nutrients in the followingconcentrations:

-   -   i) a lactate concentration of from about 0 mMol/L to about 10.0        mMol/L, optionally from about 1.0 mMol/L to about 6.0 mMol/L; or        optionally 2.0 mMol/L to about 3.0 mMol/L of the total        composition;    -   ii) a citrate concentration of from about 0 mMol/L to about 0.5        mMol/L, optionally from about 0.01 mMol/L to about 0.10 mMol/L;        or optionally 0.025 mMol/L to about 0.050 mMol/L of the total        composition;    -   iii) a phosphate concentration of from about 0 mMol/L to about        10 mMol/L, optionally from about 1 mMol/L to about 5 mMol/L; or        optionally 1.5 mMol/L to about 2.5 mMol/L of the total        composition;    -   iv) a glucose concentration of from about 0.1 mMol/L to about 25        mMol/L, optionally from about 0.1 mMol/L to about 10 mMol/L; or        optionally 0.1 mMol/L to about 0.4 mMol/L of the total        composition;

and

B. optionally, the total electrolyte concentration in the totalcomposition of the present invention comprises the individualelectrolytes in the following concentrations:

-   -   i) a potassium concentration of from about 24 mMol/L to about 28        mMol/L of the total composition;    -   ii) a sodium concentration of from about 5 mMol/L to about 10        mMol/L of the total composition;    -   iii) a magnesium concentration of from about 0.50 mMol/L to        about 0.80 mMol/L of the total composition;    -   iv) a chloride concentration of from about 23 mMol/L to about 28        mMol/L of the total composition.

In certain embodiments, ascorbic acid is present at a concentration notexceeding 0.001% w/v, optionally at from about 0.00002% w/v to about0.0001% w/v, or optionally from about 0.00001% w/v to about 0.00002%w/v, of the total composition.

In certain embodiments, the antimicrobial mixture is free of, orsubstantially free of, calcium, bicarbonate, low molecular weight aminoacids and/or zinc ions. The term “substantially free” as used hereinmeans a concentration less than 1% (or about 1%), optionally, less than0.1% (or about 0.1%), optionally less than 0.01% (or about 0.01%),optionally less than 0.001% (or about 0.0.001%), or optionally less than0.0001% (or about 0.0001%). Examples of low molecular weight amino acidsinclude, but are not limited to, L-alanine, β-alanine, α-aminoadipicacid, α-aminobutyric acid, γ-aminobutyric acid, α-aminoisobutyric acid,arginine, asparagine, aspartic acid, citrulline, creatine, glutamicacid, glycine, histidine, cysteine, leucine, lysine, norleucine,ornithine, phenylalanine, phophoserine, sarcosine, threonine and valine.

In certain embodiments, glycine is present at a concentration notexceeding 0.0010% w/v, optionally at from about 0.00001% w/v to about0.0002% w/v, or optionally from about 0.00002% w/v to about 0.0001% w/v,of the total composition.

The inventors further observed that mono- and di-saccharides such asglucose actually improve the antifungal activity of polyquaterniumcompounds such as polyquaternium 42. This is surprising as glucose agarmedium is prescribed to preculture fungi for availability inpreservative efficacy testing.

Monosaccharides suitable for use with the polyquaternium compoundseither alone, or as part of the antimicrobial mixture include, but arenot limited to (or, are selected from, or selected from the groupconsisting of), glucose, fructose, galactose, isomers thereof andmixtures thereof.

Disaccharides suitable for use with the polyquaternium compounds eitheralone or as part of the antimicrobial mixture include, but are notlimited to (or, are selected from, or selected from the group consistingof), sucrose, lactulose, lactose, maltose, α,α-trehalose, β,β-trehalose,α,β-trehalose, cellobiose, chitobiose, kojibiose. nigerose, isomaltose,sophorose, laminaribiose, gentiobiose, turanose, maltulose, palatinose,gentiobiulose, mannobiose, melibiose, melibiulose, rutinose, rutinulose,xylobiose, isomers thereof and mixtures thereof.

In certain embodiments, the mono- and/or di-saccharides is present incompositions containing the polyquaternium compound at a concentrationof from about 0.002% w/v to 1% (or about 1%) w/v, optionally at fromabout 0.002% w/v to about 0.8% w/v, or optionally at from about 0.003%w/v to about 0.4% w/v, of the total composition.

Polyol

In certain embodiments, the compositions of the present invention mayfurther comprise a polyol or combination of polyols. In certainembodiments, the presence of additional components such as thepharmaceutically active compounds may require the addition of a polyolor combination of polyols. As used herein, and unless otherwiseindicated, the term “polyol” shall refer to any compound having at leasttwo —OH groups. The polyols can be linear or circular, substituted orunsubstituted, or mixtures thereof, so long as the resultant complex iswater-soluble and pharmaceutically acceptable. Such polyol compoundsinclude sugars, sugar alcohols, sugar acids, uronic acids and mixturesthereof. In certain embodiments, the polyols are sugars, sugar alcoholsand sugar acids, including, but not limited to: mannitol, glycerin(glycerol), propylene glycol, polyethylene glycol, sorbitol and mixturesthereof. In certain embodiments, the polyols are polysorbate 80,mannitol, sorbitol, propylene glycol, polyethylene glycol, glycerin ormixtures thereof. In certain embodiments, the polyol is glycerin. Inother embodiments, the polyol is a combination of polyols such asglycerin and propylene glycol or glycerin and sorbitol.

The polyol (or combinations thereof) can optionally, be present in thecomposition of the present invention at concentrations of from about0.2% w/v to about 2.0% w/v, optionally from about 0.2% w/v to about 1.7%w/v, or optionally from about 0.4% w/v to about 1.5% w/v of the totalcomposition.

Optional Components

The compositions of the present invention may further optionallycomprise one or more additional excipients and/or one or more additionalactive ingredients. Excipients commonly used include, but are notlimited to, demulcents, tonicity agents, preservatives, chelatingagents, buffering agents (other than and in addition to the organicacids of the present invention), and surfactants. Other excipientscomprise solubilizing agents, stabilizing agents, comfort-enhancingagents, polymers, emollients, pH-adjusting agents (other than and inaddition to the organic acids of the present invention), and/orlubricants. Any of a variety of excipients may be used in thecompositions of the present invention including water, mixtures of waterand water-miscible solvents, such as vegetable oils or mineral oilscomprising from 0.5% to 5% non-toxic water-soluble polymers, naturalproducts, such as agar and acacia, starch derivatives, such as starchacetate and hydroxypropyl starch, and also other synthetic products suchas polyvinyl alcohol, polyvinylpyrrolidone, polyvinyl methyl ether,polyethylene oxide, and preferably cross-linked polyacrylic acid andmixtures thereof.

Demulcents or soothing agents used with embodiments of the presentinvention, in addition to the cellulose derivatives include, but are notlimited to, glycerin, polyvinyl pyrrolidone, polyethylene oxide,polyethylene glycol, propylene glycol and polyacrylic acid. In certainembodiments, propylene glycol and polyethylene glycol 400 are thedemulcents. In certain embodiments, glycerin, in addition to its use asa tonicity adjusting agent, can also act as a demulcent.

Tonicity-adjusting agents may also be, optionally, used in thecompositions of the present invention. Suitable tonicity-adjustingagents include, but are not limited to, mannitol, sodium chloride,glycerin, and the like. Suitable buffering agents include, but are notlimited to, phosphates, borates, acetates and the like, and aminoalcohols such as 2-amino-2-methyl-1-propanol (AMP), salts of any of theabove and mixtures of any of the above mentioned agents.

Suitable surfactants include, but are not limited to, ionic and nonionicsurfactants (though nonionic surfactants are preferred), RLM 100, POE 20cetylstearyl ethers such as Procol® CS20, poloxamers such as Pluronic®F68, and block copolymers such as poly(oxyethylene)-poly(oxybutylene)compounds set forth in U.S. Patent Application Publication No.2008/0138310 entitled “Use of PEO-PBO Block Copolymers in OphthalmicCompositions” filed Dec. 10, 2007 (which publication is hereinincorporated by reference).

Also useful herein are polyethoxylated castor oil compounds classifiedas PEG-2 to PEG-200 castor oils, as well as those classified as PEG-5 toPEG-200 hydrogenated castor oils. Such polyethoxylated castor oilsinclude those manufactured by Rhone-Poulenc (Cranbury, N.J.) under theAlkamuls® brand, those manufactured by BASF (Parsippany, N.J.) under theCremophor® brand, and those manufactured by Nikko Chemical Co., Ltd.(Tokyo, Japan) under the Nikkol brand. In certain embodiments, thepolyethoxylated castor oils are those classified as PEG-15 to PEG-50castor oils or, optionally, PEG-30 to PEG-35 castor oils. In someembodiments, polyethoxylated castor oils known as Cremophor® EL andAlkamuls® EL-620 are used. In other embodiments, polyethoxylatedhydrogenated castor oils classified as PEG-25 to PEG-55 hydrogenatedcastor oils are used. In one embodiment, the polyethoxylatedhydrogenated castor oil is PEG-40 hydrogenated castor oil, supplied asLumulse GRH-40 by VANTAGE (GURNEE, Ill., USA).

In general, the present invention can include one or morepolyethoxylated castor oils in an amount from about 0.02% to about 20%by weight (wt %) of the total composition. In certain embodiments, oneor more polyethoxylated castor oils may be used in an amount of fromabout 0.05 wt % to about 5 wt %, or, optionally, from about 0.1 wt % toabout 2 wt % of the total composition. Mixtures of any of the abovepolyethoxylated castor oils and polyethoxylated hydrogenated castor oilscan also be used.

Compositions of the present invention are ophthalmologically suitablefor application to a subject's eyes. The term “aqueous” used indescribing an aqueous formulation, or an aqueous component of the totalcomposition, wherein the excipient is greater than about 50%, optionallygreater than about 75%, or optionally greater than about 90% by weightwater. These drops may be delivered from a single dose ampoule which maypreferably be sterile and thus render microcidal orbacteriostatic/fungistatic components of the formulation unnecessary.Alternatively, the drops may be delivered from a multi-dose bottle whichmay preferably comprise a device which extracts any preservative fromthe composition as it is delivered, such devices being known in the art.

In certain embodiments, the compositions of the present invention areisotonic, or slightly hypotonic in order to combat any hypertonicity oftears caused by evaporation and/or disease. This may require a tonicityagent to bring the osmolality of the formulation to a level at or near210-320 milliosmoles per kilogram (mOsm/kg). The compositions of thepresent invention generally have an osmolality in the range of 220-320mOsm/kg, or, optionally, have an osmolality in the range of 235-300mOsm/kg. The ophthalmic compositions will generally be formulated assterile aqueous solutions.

In a useful embodiment, the compositions of the present inventioninclude hydrophobic components. Any suitable hydrophobic component maybe employed in the present invention. In one embodiment, the hydrophobiccomponent may be considered as comprising a discontinuous phase in thecompositions of the present invention, for example, oil-in-wateremulsions.

The hydrophobic component may be present in an effective amount, forexample, in an amount of up to about 1.0% by weight or about 1.5% byweight of the total composition.

In certain embodiments, the hydrophobic component comprises one or moreoily materials. Examples of useful oil materials include, withoutlimitation, vegetable oils, animal oils, mineral oils, synthetic oilsand the like and mixtures thereof. In one embodiment, the hydrophobiccomponent comprises one or more higher fatty acid glycerides. In anotherembodiment, the hydrophobic component comprises castor oil. Otherembodiments, the oil component is combined with the above mentionedsurfactants (e.g., in certain embodiments, the polyethoxylated castoroil and/or polyethoxylated hydrogenated castor oil surfactants) in theaqueous formulations to form emulsions.

In one embodiment, the presently useful compositions areself-emulsifying which, when exposed to an aqueous medium, form fineoil-in-water emulsions with little or no agitation. Additionally,emulsions may be prepared by combining a self-emulsifyingpre-concentrate with an aqueous medium. Previously-disclosedself-emulsifying systems include those comprising mixtures of (i)medium-chain triglycerides and nonionic surfactants, (ii) vegetable oilsand partial glycerides, such as polyglycolized glycerides ormedium-chain mono- and diglycerides, or (iii) vegetable oils andnonionic surfactants such as polysorbate 80, PEG-25 glyceryl trioleate,polyethoxylated castor oils and/or polyethoxylated hydrogenated castoroils.

The compositions of the present invention can also be used to administerpharmaceutically active compounds. Such compounds include, but are notlimited to, (or selected from or selected from the group consisting of)glaucoma therapeutics, pain relievers, anti-inflammatory,vaso-constrictors, dry eye relievers and anti-allergy medications, andanti-infectives. More specific examples of pharmaceutically activecompounds include betaxolol, timolol, pilocarpine or pharmaceuticallyacceptable salts thereof; carbonic anhydrase inhibitors orpharmaceutically acceptable salts thereof; prostglandins; dopaminergicantagonists; post-surgical antihypertensive agents, such as para-aminoclonidine (apraclonidine) or pharmaceutically acceptable salts thereof;anti-infectives such as ciprofloxacin, moxifloxacin, tobramycin orpharmaceutically acceptable salts thereof; non-steroidal and steroidalanti-inflammatories, such as naproxen, diclofenac, nepafenac, suprofen,ketorolac, tetrahydrocortisol, dexamethasone or pharmaceuticallyacceptable salts thereof; dry eye therapeutics or pharmaceuticallyacceptable salts thereof such as PDE4 inhibitors; vaso-contrictors suchas tetrahydrozoline, naphazoline, oxymetazoline, ephedrine,phenylephrine or pharmaceutically acceptable salts thereof; anti-allergymedications or pharmaceutically acceptable salts thereof such as H1/H4inhibitors, H4 inhibitors, olopatadine; and dry eye relievers such astamarind seed extract, hyaluronic acid and guar gum (including highperformance guar gum); or mixtures of any of the above mentioned activesor categories of actives.

In certain embodiments, the compositions of the present inventionfurther include one of more retinoids. Retinoids include Vitamin A(retinol), retinoic acid, and retinyl palmitate as well as relatedcompounds that are synthetic or naturally occurring cellular componentsor metabolites. The effects of RA and synthetic derivatives are mediatedby two classes of nuclear receptors, the retinoic acid receptors whichbelong to the erbA-related steroid/thyroid nuclear receptor superfamilyand the retinoid X receptors which also belong to the same super familyof steroid/thyroid hormones (Gorodeski, et al., Am. J. Physiol. Cell.Physiol. 275, 758-765 (1998).

Vitamin A and related retinoids are involved in the maintenance ofmucosal membranes via control of the proliferation and differentiationof epithelial cells. A deficiency of retinoids results in a gradualchange of the ocular mucosa to a non-secretory keratinized epithelium.(Kobayashi, et al., Ophthalmologica, 211, 358-361 (1997)). Retinoic acidplays a fundamental role in cell proliferation, and cell differentiationand it may also prevent malignant transformation (Darmon, 1991, Sem.Dev. Biol. 2:219).

Retinoids have been utilized to treat a number of conditions involvingkeratinization of epithelial tissue, including: acne vulgaris,psoriasis, wound healing and premalignant lesions (Kligman, A., Cutis,39, 486-488 (1987). Formulations containing retinoids have also beenutilized to treat ocular disorders involving the epithelium, such as dryeye, Stevens-Johnson syndrome (Kobayashi, et al., Ophthalmologica, 211,358-361 (1997); Selek, et al., Eur. J. Ophthalmol, 10, 121-127 (2000)and Kim, et al., Amer. J. Oph, 147, 206-213.e3 (2009)). Topical retinoidformulations include ointments and liquid formulations that may beapplied 2-4 times per day for one or more months. Increases in gobletcell density in ocular mucosal tissue, tear break up time and Schirmerscore measurements have been noted following topical retinoid therapy.

In certain embodiments, the compositions of the present inventionfurther comprise one or more fatty acid esters such as 1-3 carbonmonohydric or 4-10 carbon polyol esters of: alpha-linolenate,dihomogamma-linolenic acid, gamma-linolenate, eicosapentaenoic acid ordocosahexaenoic acid (e.g., ethyl alpha-linolenate or ethylgamma-linolenate). Mixtures of any such fatty acid esters may also beused herein. Suitable monohydric and/or polyol fatty acid esters aredetailed in US patent publications US20130005805A1 and US20140364400A1,each of which are herein incorporated by in its entirety.

It is also contemplated that the concentrations of the ingredientscomprising the formulations of the present invention can vary. A personof ordinary skill in the art would understand that the concentrationscan vary depending on the addition, substitution, and/or subtraction ofingredients in a given formulation.

In certain embodiments, the compositions of the present invention arebuffered, using buffering agents, such that the compositions maintain apH of from about 5.0 to a pH of about 8.0, optionally a pH of from about6.5 to a pH of about 8.0. Topical formulations (particularly topicalophthalmic formulations, as noted above) are preferred which have aphysiological pH matching the tissue to which the formulation will beapplied or dispensed.

In certain embodiments, the compositions of the present invention is inthe form of eye-drop solution, eye wash solution, contact lens packingsolutions, contact lens lubricating, rewetting and/or rinsing solution,spray, mist or any other manner of administering a composition to theeye.

In particular embodiments, the composition of the present invention areformulated for administration at any frequency of administration,including once a week, once every five days, once every three days, onceevery two days, twice a day, three times a day, four times a day, fivetimes a day, six times a day, eight times a day, every hour, or greaterfrequency. Such dosing frequency is also maintained for a varyingduration of time depending on the therapeutic needs of the user. Theduration of a particular therapeutic regimen may vary from one-timedosing to a regimen that extends for months or years. One of ordinaryskill in the art would be familiar with determining a therapeuticregimen for a specific indication.

Examples

The compositions of the present invention as described in followingexamples illustrate specific embodiments of compositions of the presentinvention, but are not intended to be limiting thereof. Othermodifications can be undertaken by the skilled artisan without departingfrom the spirit and scope of this invention.

TABLE 1 Comparative and Inventive examples of the Compositions of thePresent Invention 1C (Inventive 1E (Inventive Example) 1D (InventiveExample) Useful for Relief Example) Useful for Relief 1A (Comparative 1B(Comparative of Dry Eye Useful for Relief of of Dry Eye Example)Example) Irritation (with or Dry Eye Irritation Irritation (with or DryEye Dry Eye without Contact (with or without without ContactCompositions Compositions Lenses) Contact Lenses) Lenses) amount amountamount amount amount per per per per per batch batch batch batch batchINGREDIENT % w/w (gms) % w/w (gms) % w/w (gms) % w/w (gms) % w/w (gms)Sodium Hyaluronate¹ 0.25 1.25 0.1 0.2 0.10 1.00 0.120 1.20 0.120 0.60Tamarind Seed 0.25 1.25 0.10 1.00 0.200 2.00 0.200 1.00 Polysaccharide²Polyethylene Glycol 1.118 11.18 1.118 5.59 400³ Glycerin 0.2502 2.5020.2502 1.251 Hypromellose E3 0.3 0.6 0.30 3.0 0.198 1.98 0.198 0.992910⁴ Boric Acid⁵ 0.80 8.0 0.80 4.0 Sodium Borate⁶ 0.045 0.45 DisodiumPhosphate⁷ 0.027 0.27 0.027 0.135 Sodium Citrate 0.20 2.0 0.20 1.0Dihydrate⁸ Sodium Chloride⁹ 0.87 4.35 0.87 1.74 0.88 8.8 PotassiumChloride¹⁰ 0.10 1.0 0.179 0.895 50% Aqueous 0.057 0.57 0.057 0.285Solution of Sodium Lactate¹¹ Magnesium Chloride¹² 0.013 0.13 0.013 0.065Glucose¹³ 0.0036 0.036 0.0036 0.018 Glycine¹⁴ 0.00002 0.0002 0.000020.0001 Ascorbic Acid¹⁵ 0.00001 0.0001 0.00001 0.00005 1N Sodium 0.0030.015 0.003 0.006 0.001 0.01 Hydroxide¹⁶ Disodium Edetate¹⁷ 0.01 0.10.05 0.25 Polyquaternium 42¹⁸ 0.0030 0.015 Purified Water 98.627 493.13598.727 197.454 98.619 986.20 96.8517 968.52 96.78117 483.91 total100.00% 500.00 g 100.00% 200.00 g 100.00% 1000.00 g 100.00% 1000.00 g100.00% 500.00 g ¹Research Grade, HA15M Supplied by LIFECORE (CHASKA,MINNESOTA US). ²Supplied by FARMIGEA (OSPEDALETTO, ITALY) ³Supplied byClariant Produkte (BURGKIRCHEN, GERMANY) ⁴Hydroxypropylmethyl cellulosesupplied by DOW CHEMICAL (PLAQUEMINE, LOUISIANA, USA) ⁵Supp1ied by MerckKGaA (DARMSTADT, GERMANY) ⁶5upp1ied by Merck KGaA (DARMSTADT, GERMANY)⁷Supplied by Merck KGaA (DARMSTADT, GERMANY) ⁸Supplied by Merck KGaA(DARMSTADT, GERMANY) ⁹Supplied by Caldic (DUSSELDORF, GERMANY)¹⁰Potassium Chloride was supplied by KGaA (DARMSTADT, GERMANY)¹¹Supplied as Sodium Lactate (50% aqueous) by Merck KGaA (DARMSTADT,GERMANY) ¹²Supplied by KGaA (DARMSTADT, GERMANY) ¹³Supplied by RoquetteFreres (LASTREM, FRANCE) ¹⁴Supplied by Merck KGaA (DARMSTADT, GERMANY)¹⁵Supplied by DSM NUTRITIONAL Products (DRAKEMYRE, SCOTLAND, UK)¹⁶Supplied by VWR (RADNER, PA) ¹⁷Supplied by Merck NV/SA (OVERIJSE,BELGIUM) ¹⁸Supplied as Polyquaternium 42 (33% aqueous) by DSMBIOMEDICAL, (BERKELEY, CA)The procedure for preparing solution 1A was as follows:

-   1. To an 800 ml beaker is added 450 grams of Purified Water USP.-   2. To the composition of step 1 is added 1.25 g of Sodium    Hyaluronate. The solution is mixed until the Sodium Hyaluronate    dissolved.-   3. To the solution of step 2 is added 1.25 g of Tamarind Seed    Polysaccharide. The solution is mixed until the Tamarind Seed    Polysaccharide dissolved.-   4. Next is added 4.35 g of Sodium Chloride to the solution of    step 3. The solution is mixed until all the Sodium Chloride is    dissolved.-   5. To the solution of Step 4, 0.15 gram of a premixed solution of 1    gram of 1 N Sodium Hydroxide solution in 9 grams of Purified Water    is added.-   6. Additional water is added to the solution of step 5 to bring the    weight of the solution to a total of 500.00 grams and the solution    is mixed for an additional 10 minutes.    Results: The solution has a surface tension of 68.06, as measured by    the Rame-Hart—DROPimage Advanced Software Pendant Drop Method    described above, which is greater than about 40.8 dynes/cm to 51.9    dynes/cm of the present invention and is not expected to have rapid    and extensive rewetting of eyes because of such high surface    tension.    The procedure for preparing solution 1B was as follows:-   1. To a 500 ml beaker is added 160 grams of Purified Water USP.-   2. To the composition of step 1 is added 0.2 g of Sodium    Hyaluronate. The solution is mixed until the Sodium Hyaluronate    dissolved.-   3. To the solution of step 2 is added 0.6 g of Hypromellose E3    Premium. The solution is mixed until the Hypromellose E3 Premium    dissolved.-   4. Next is added 1.74 g of Sodium Chloride to the solution of    step 3. The solution is mixed until all the Sodium Chloride is    dissolved.-   5. To the solution of Step 4, 0.06 gram of a premixed solution of 1    gram of 1 N Sodium Hydroxide solution in 9 grams of purified water    is added.-   6. Additional water is added to the solution of step 6 to bring the    weight of the solution to a total of 200.00 grams and the solution    is mixed for an additional 10 minutes.    Results: The solution has a viscosity of 24 cps as measured by the    AR2000 Flow Test Method described above, which falls outside of the    about 50 cps to about 100 cps viscosity range of the present    invention and is not expected to have sufficient substantivity    and/or moisturization to permit retention on the ocular surface for    improved tear stability for dry eye relief.    The procedure for preparing solution 1C was as follows:-   1. To a 1500 ml beaker is added 900 grams of Purified Water USP.-   2. To the composition of step 1 is added 0.1 g of Sodium    Hyaluronate. The solution is mixed until the Sodium Hyaluronate    dissolved.-   3. To the solution of step 2 is added 0.1 g of Tamarind Seed    Polysaccharide. The solution was mixed until the Tamarind Seed    Polysaccharide dissolved.-   4. To the solution of step 3 is added 0.3 g of Hypromellose E3    Premium. The solution was mixed until the Hypromellose E3 Premium    dissolved.-   5. Next is added 8.8 g of Sodium Chloride to the solution of step 4.    The solution is mixed until all the Sodium Chloride is dissolved.-   6. To the solution of Step 5, 0.10 gram of a premixed solution of 1    gram of 1 N Sodium Hydroxide dissolved in 9 grams of Purified Water.-   7. Additional water is added to the solution of step 6 to bring the    weight of the solution to a total of 1000.00 grams and the solution    is mixed for an additional 10 minutes.    Results: The solution has a viscosity 86.0 cps., as measured by the    AR2000 Flow Test Method described above, which falls within the    about 50 cps to about 100 cps viscosity range of the present    invention and is expected to have sufficient substantivity and/or    moisturization to permit retention on the ocular surface for    improved tear stability for dry eye relief    The procedure for preparing solution 1D was as follows:-   1. To a 1500 ml beaker is added 800 grams of Purified Water USP.-   2. To the beaker of step 1 is added 1.2 g of Sodium Hyaluronate. The    solution is mixed until the Sodium Hyaluronate is dissolved.-   3. To the solution of step 2 is added 0.2 g of Tamarind Seed    Polysaccharide. The solution is mixed until the Tamarind Seed    Polysaccharide is dissolved.-   4. To the solution of step 3 is added 1.98 g of Hypromellose E3    Premium. The solution is mixed until the Hypromellose E3 Premium is    dissolved.-   5. Into a separate 150 ml beaker is added 95 g of Purified Water.-   6. To the beaker in step 5 is added 0.02 grams of Glycine and 0.01    grams of Ascorbic acid. The solution is mixed until the Glycine and    Ascorbic acid are dissolved.-   7. An additional 4.97 grams of water is added to the solution of    step 6 and mixed until the solution was uniform.-   8. To the solution of Step 4 is added 2.0 grams of Sodium Citrate.    The Sodium Citrate is mixed into the solution for at least 10    minutes until dissolved.-   9. To the solution of Step 8 are added the following ingredients    while mixing, allowing time for each to dissolve completely before    adding the next: 0.27 grams of Disodium Phosphate, 0.13 grams of    Magnesium Chloride, 1.0 grams of Potassium Chloride, 0.036 grams of    Glucose, and 0.45 grams of Sodium Borate, allowing each ingredient    to mix before adding the next.-   10. To the solution of Step 9, 2.5 grams of Glycerin and 11.18 grams    of Polyethylene Glycol 400 are slowly added while mixing, allowing    for each ingredient to completely dissolve before the next    ingredient is added.-   11. To the solution of Step 10, 8.0 grams of Boric acid and 0.57 g    of Sodium Lactate are slowly added while mixing and mixed until    completely dissolved.-   12. To the solution of Step 11 is added 1.0 gram of the solution    prepared in step 7.-   13. To the solution of step 12 is added 0.1 grams of Disodium    Edetate.-   14. The solution of step 13 is mixed until completely dispersed.-   15. Sufficient water is added to solution of step 14 to bring the    weight of the solution of Step 13 to 1000.00 grams and the solution    was mixed for an additional 10 minutes.    Results: The solution has a viscosity of 72.2 cps, as measured by    the AR2000 Flow Test Method described above, which falls within the    about 50 cps to about 100 cps viscosity range of the present    invention and is expected to have sufficient substantivity and/or    moisturization to permit retention on the ocular surface for    improved tear stability for dry eye relief    The procedure for preparing solution 1E was as follows:-   1 To a 1000 ml beaker was added 400 grams of Purified Water USP.-   2. To the beaker of step 1 was added 0.6 g of Sodium Hyaluronate.    The solution was mixed until the Sodium Hyaluronate dissolved.-   3. To the solution of step 2 is added 0.1 g of Tamarind Seed    Polysaccharide. The solution is mixed until the Tamarind Seed    Polysaccharide is dissolved.-   4. To the solution of step 3 is added 0.99 g of Hypromellose E3    Premium. The solution is mixed until the Hypromellose E3 Premium is    dissolved.-   5. Into a separate 150 ml beaker is added 95 g of Purified Water.-   6. To the beaker in step 5 is added 0.01 grams of Glycine and 0.005    grams of Ascorbic acid. The solution is mixed until the Glycine and    Ascorbic acid are dissolved.-   7. An additional 4.97 grams of water is added to the solution of    step 6 and mixed until the solution was uniform.-   8. To the solution of Step 4 is added 1.0 grams of Sodium Citrate.    The Sodium Citrate is mixed into the solution for at least 10    minutes until dissolved.-   9. To the solution of Step 8 are added the following ingredients    while mixing, allowing time for each to dissolve completely before    adding the next: 0.135 grams of Disodium Phosphate, 0.065 grams of    Magnesium Chloride, 0.895 grams of Potassium Chloride, and 0.018    grams of Glucose, allowing each ingredient to mix before adding the    next.-   10. To the solution of Step 9, 1.25 grams of Glycerin and 5.59 grams    of Polyethylene Glycol 400 are slowly added while mixing, allowing    for each ingredient to completely dissolve before the next    ingredient is added.-   11. To the solution of Step 10, 4.0 grams of Boric acid and 0.285 g    of Sodium Lactate are slowly added while mixing and mixed until    completely dissolved.-   12. To the solution of Step 11 is added 1.0 gram of the solution    prepared in step 7.-   13. To the solution of step 12 is added 0.25 grams of Disodium    Edetate.-   14. The solution of step 13 is mixed until completely dispersed.-   15. To the solution in step 14 is added 0.045 grams of a 33%    solution of Polyquaternium 42 in water.-   16. Sufficient water is added to solution of step 15 to bring the    weight of the solution of Step 15 to 500.00 grams and the solution    is mixed for an additional 10 minutes.    Results: The solution has a viscosity of 68.6 cps as measured by the    AR2000 Flow Test Method described above, within the about 50 cps to    about 100 cps viscosity range of the present invention and is    expected to have sufficient substantivity and/or moisturization to    permit retention on the ocular surface for improved tear stability    for dry eye relief.

TABLE 2 Prophetic Examples of the Compositions of the Present Invention2A 2B 2C Useful for Relief of Dry Useful for Relief of Useful for Reliefof Eye Irritation Dry Eye Irritation Dry Eye Irritation amount amountamount per batch per batch per batch INGREDIENT % w/w (gms) % w/w (gms)% w/w (gms) Sodium 0.10 1.0 0.10 1.0 0.10 1.0 Hyaluronate Tamarind Seed0.10 1.0 0.20 2.0 0.10 1.0 Polysaccharide Hypromellose 0.30 3.0 0.30 3.00.30 3.0 2910 Polyethylene 0.25 2.5 0.25 2.5 0.25 2.5 Glycol 400 BoricAcid 0.60 6.0 0.60 6.0 0.60 6.0 Sodium Borate 0.035 0.35 0.05 0.50 0.050.50 Sodium Chloride 0.05 0.50 0.05 0.50 0.05 0.50 Calcium Chloride0.006 0.060 0 0 0 0 Magnesium 0.006 0.060 0 0 0 0 Chloride Potassium0.14 1.40 0 0 0 0 Chloride Sodium Citrate 0 0 0.65 6.50 0.65 6.50Dihydrate Super refined 0.625 6.25 0.625 6.25 0.625 6.25 Castor OilLumulse GRH-40 0.50 5.0 0.50 5.0 0.50 5.0 Ethyl linolenate 0 0 0.05020.502 0.0502 0.502 Retinyl Palmitate 0 0 0.0502 0.502 0.0502 0.502Sodium Chlorite 0.014 0.140 0 0 0 0 Polyquaternium 0 0 0.0090 0.090 0 042 (33% aqueous) Purified Water* total 100.00% 1000.0 g 100.00% 1000.0 g100.00% 1000.0 g *q.s to 100% w/wFor Examples 2A-2C: The Sodium Hyaluronate can be supplied by CONTIPROA.S. (DOLNI, DOBROUC, CZECH REPUBLIC).For Examples 2A-2C: The Tamarind Seed Extract can be supplied by INDENA(MILAN, ITALY).For Examples 2A-2C: The Hypromellose 2910 is HPMC E3 Premium can besupplied by DOW CHEMICAL (PLAQUAMINE, LOUISIANA, USA).For Examples 2A-2C: The Polyethylene Glycol 400 can be supplied byClariant Produkte (BURGKIRCHEN, GERMANY).For Examples 2A-2C: The Boric Acid can be supplied by Merck KGaA(DARMSTADT, GERMANY).For Examples 2A-2C: The Sodium Borate can be supplied by Merck KGaA(DARMSTADT, GERMANY).For Examples 2A-2C: The Sodium Chloride can be supplied by Caldic(DUSSELDORF, GERMANY).For Examples 2A: The Calcium Chloride Dihydrate can be supplied by MerckKGaA (DARMSTADT, GERMANY).For Examples 2A: The Magnesium Chloride can be supplied by KGaA(DARMSTADT, GERMANY).For Examples 2A: The Potassium Chloride can be supplied by KGaA(DARMSTADT, GERMANY).For Example 2A: The Sodium Chlorite Dihydrate can be supplied by Oxychem(WICHITA, Kans., USA)For Example 2B: The Polyquaternium-42 (33% aqueous) can be supplied byDSM BIOMEDICAL (BERKELEY, Calif., USA)For Examples 2A-2C: The Lumulse GRH-40 can be supplied by VANTAGE(GURNEE, Ill., USA).For Examples 2A-2C: The Super refined Castor Oil can be supplied byCRODA (EDISON, N.J., USA).For Examples 2B-2C: The Ethyl linolenate can be supplied bySIGMA-ALDRICH (ST. LOUIS, Mo., USA).For Examples 2B-2C: The Retinyl Palmitate can be supplied bySIGMA-ALDRICH (ST. LOUIS, Mo., USA).For Examples 2B-2C: The Sodium Citrate Dihydrate can be supplied byMerck KGaA (DARMSTADT, GERMANY).The procedure for preparing solution 2A can be as follows:

-   1. To a 50 ml beaker is added 5.0 grams of Lumuluse GRH-40-   2. While mixing, 6.25 grams of Super refined Castor Oil is added.-   3. The above is mixed until homogeneous.-   4. In a separate 1500 ml beaker is added 900 grams of Purified    Water.-   5. To the above is added 1.0 gram of Sodium Hyaluronate. The    solution is mixed to fully dissolve the Sodium Hyaluronate.-   6. To the above is added 1.0 gram of Tamarind Seed Polysaccharide.    -   The solution is mixed until the Tamarind Seed Polysaccharide is        fully dissolved.-   7. To the above solution is next added 3.0 grams of Hypromellose    2910 E3 Premium.-   8. The solution is mixed until fully dissolved.-   9. The following ingredients are next added sequentially, allowing    for each to dissolve before adding the next: 2.5 grams Polyethylene    Glycol 400, 6.0 grams Boric acid, 0.035 gram Sodium Borate, 0.5 gram    Sodium Chloride, 0.06 gram Calcium Chloride, 0.06 gram Magnesium    Chloride, and 1.40 grams of Potassium Chloride.-   10. The contents of step 3 are added and mixed until uniform using a    homogenizer.-   11. Next is added 0.14 gram of Sodium Chlorite.-   12. The solution is brought to 1000.0 grams using Purified Water USP    and mixed for 10 minutes to be fully uniform.-   13. The solution is filtered using a 0.22 micron hydrophilic filter.    The procedure for preparing solution 2B is as follows:-   1. To a 50 ml beaker is added 5.0 grams of Lumuluse GRH-40-   2. While mixing, 6.25 grams of Super refined Castor Oil is added.-   3. To the above is added 0.502 grams of Ethyl Linolenate and 0.502    gram of Retinyl Palmitate.-   4. The uniform solution is set aside for future use.-   5. In a separate 1500 ml beaker is added 900 grams of Purified    Water.-   6. To the above is added 1.0 grams of Sodium Hyaluronate. The    solution is mixed to fully dissolve the Sodium Hyaluronate.-   7. Next, 2.0 grams of Tamarind Seed Polysaccharide is added. The    solution is mixed to fully dissolve the Tamarind Seed    Polysaccharide.-   8. To the above is added 3.0 grams of Hypromellose 2910 E3 Premium.-   9. The solution is mixed to fully dissolve the HPMC.-   10. The following ingredients are next added sequentially, allowing    for each to dissolve before adding the next: 2.5 grams Polyethylene    Glycol 400, 6.0 grams Boric acid, 0.5 gram Sodium Borate, 0.5 gram    Sodium Chloride, 6.50 grams of Sodium Citrate Dihydrate, and 0.090    grams of Polyquaternium-42 (33% aqueous).-   11. The contents of step 3 are added and mixed until uniform using a    homogenizer.-   12. The solution is brought to 1000.0 grams using Purified Water USP    and mixed for 10 minutes to be fully uniform.-   13. The solution is filtered using a 0.22 micron filter.    The procedure for preparing solution 2C is as follows:-   1. To a 50 ml beaker is added 5.0 grams of Lumuluse GRH-40-   2. While mixing, 6.25 grams of Super refined Castor Oil is added.-   3. To the above is added 0.502 grams of Ethyl Linolenate and 0.502    gram of Retinyl Palmitate.-   4. The uniform solution is set aside for future use.-   5. In a separate 1500 ml beaker is added 900 grams of Purified    Water.-   6. To the above is added 1.0 grams of Sodium Hyaluronate. The    solution is mixed to fully dissolve the Sodium Hyaluronate.-   7. Next, 1.0 grams of Tamarind Seed Polysaccharide is added. The    solution is mixed to fully dissolve the Tamarind Seed    Polysaccharide.-   8. To the above is added 3.0 grams of Hypromellose 2910 E3 Premium.-   9. The solution is mixed to fully dissolve the HPMC.-   10. The following ingredients are next added sequentially, allowing    for each to dissolve before adding the next: 2.5 grams Polyethylene    Glycol 400, 6.0 grams Boric acid, 0.5 gram Sodium Borate, 0.5 gram    Sodium Chloride, and 6.50 grams of Sodium Citrate Dihydrate.-   11. The contents of step 3 are added and mixed until uniform using a    homogenizer.-   12. The solution is brought to 1000.0 grams using Purified Water USP    and mixed for 10 minutes to be fully uniform.-   13. The solution is filtered using a 0.22 micron filter.

Embodiments of the Present Invention

1. A composition, comprising:

-   -   a polymer mixture comprising        -   i. a cellulose derivative;        -   ii a tamarind seed extract; and        -   iii hyaluronic acid;    -   optionally, an oil component;    -   optionally, a surfactant; and    -   optionally, an aqueous component    -   wherein the cellulose derivative, tamarind seed extract and        hyaluronic acid are combined at a ratio of: 1 to 10 parts        cellulose derivative:1 to 4 parts tamarind seed extract:1 to 2        parts hyaluronic acid, to form the polymer mixture.        2. The composition of embodiment 1 wherein the cellulose        derivative is selected from (or, selected from the group        consisting of) hydroxyalkyl cellulose polymers, alkyl        hydroxyalkyl cellulose polymers; methyl cellulose; methyl        cellulose derivatives; hydroxymethycellulose derivatives; and        mixtures thereof.        3. The composition of any one of or combination of embodiments 1        and 2, wherein the hydroxyalkyl cellulose polymers are selected        from (or, selected from the group consisting of) hydroxyethyl        cellulose, hydroxypropyl cellulose and mixtures thereof.        4. The composition of any one of or combination of embodiments 1        to 3, wherein the alkyl hydroxyalkyl cellulose polymers is cetyl        hydroxyethyl cellulose.        5. The composition of any one of or combination of embodiments 1        to 4, wherein the methyl cellulose derivative is selected from        (or, selected from the group consisting of) carboxymethyl        cellulose, hydroxmethyl cellulose, a hydroxymethyl cellulose        derivative or mixtures thereof.        6. The composition of any one of or combination of embodiments 1        to 5, wherein the hydroxymethyl cellulose derivative is selected        from (or, selected from the group consisting of) hydroxypropyl        methylcellulose, hydroxybutyl methyl cellulose or mixtures        thereof.        7. The composition of any one of or combination of embodiments 1        to 6, wherein the total concentration of the polymer mixture of        cellulose derivative, tamarind seed extract and hyaluronic acid        is greater than about 0.4% to about 0.9%, by weight, of the        total composition of the present invention.        8. The composition of any one of or combination of embodiments 1        to 7, the total concentration of non-ionic and anionic polymer        of the compositions is from (or greater than) 0.4% (or about        0.4%) to about 1.0% (or about 1.0%), by weight, of the total        composition of the present invention.        9. The composition of any one of or combination of embodiments 1        to 8, wherein the surface tension of the composition ranges from        about 40.8 dynes/cm to 51.9 dynes/cm as measured by the        Rame-Hart—DROPimage Advanced Software Pendant Drop Method        described in the specification.        10. The composition of any one of or combination of embodiments        1 to 9, wherein the rate of moisture loss for the composition is        less than 1 mg/3 minutes at 37° C. and 70% relative humidity as        measured by the DVS Intrinsic Measurement System and        DVS-Intrinsic Control Software Method described in the        specification.        11. The composition of any one of or combination of embodiments        1 to 10, wherein the composition has a viscosity of from about        30 to 100 cps at zero shear as measured by the AR2000 Flow Test        Method described in the specification.        12. The composition of any one of or combination of embodiments        1 to 11, wherein the compositions have a viscosity of less than        30 cps at the shear rate of blinking ( 1/100 sec.) as measured        by the AR2000 Flow Test Method described in the specification.        13. The composition of any one of or combination of embodiments        1 to 12, wherein the composition has an elastic modulus G′        greater than 0.70 (or about 0.70) Pascals and a phase angle δ of        from about 40° to about 65° as measured by the Bohlin CVOR        Rheometer Visco-Elastic Property Test Method described in the        specification.        14. The composition of any one of or combination of embodiments        1 to 13, wherein the composition has:    -   i. a surface tension ranging from about 40.8 dynes/cm to 51.9        dynes/cm as measured by the Rame-Hart—DROPimage Advanced        Software Pendant Drop Method described in the specification;    -   ii. a rate of moisture loss of less than 1 mg/3 minutes at        37° C. and 70% relative humidity as measured by the DVS        Intrinsic Measurement System and DVS-Intrinsic Control Software        Method described in the specification;    -   iii. a viscosity of from about 30 to 100 cps at zero shear and a        viscosity of less than 30 cps at the shear rate of blinking (        1/100 sec.) as measured by the AR2000 Flow Test Method described        in the specification; and    -   iv. an elastic modulus G′ greater than 0.70 (or about 0.70)        Pascals and a phase angle δ of from about 40° to about 65° as        measured by the Bohlin CVOR Rheometer Visco-Elastic Property        Test Method described in the specification.

What is claimed is:
 1. A composition, comprising: a polymer mixturecomprising i. a cellulose derivative; ii. a tamarind seed extract; andiii hyaluronic acid; wherein the cellulose derivative, tamarind seedextract and hyaluronic acid are combined at a ratio of: 1 to 10 partscellulose derivative:1 to 4 parts tamarind seed extract:1 to 2 partshyaluronic acid, to form the polymer mixture.
 2. The composition ofclaim 1 wherein the cellulose derivative is selected from (or, selectedfrom the group consisting of) hydroxyalkyl cellulose polymers, alkylhydroxyalkyl cellulose polymers; methyl cellulose; methyl cellulosederivatives; hydroxymethycellulose derivatives; and mixtures thereof. 3.The composition of claim 2, wherein the hydroxyalkyl cellulose polymersare selected from (or, selected from the group consisting of)hydroxyethyl cellulose, hydroxypropyl cellulose and mixtures thereof. 4.The composition of claim 2, wherein the alkyl hydroxyalkyl cellulosepolymers is cetyl hydroxyethyl cellulose.
 5. The composition of claim 2,wherein the methyl cellulose derivative is selected from (or, selectedfrom the group consisting of) carboxymethyl cellulose, hydroxmethylcellulose, a hydroxymethyl cellulose derivative or mixtures thereof. 6.The composition of claim 5, wherein the hydroxymethyl cellulosederivative is selected from (or, selected from the group consisting of)hydroxypropyl methylcellulose, hydroxybutyl methyl cellulose or mixturesthereof.
 7. The composition of claim 1, wherein the total concentrationof the polymer mixture of cellulose derivative, tamarind seed extractand hyaluronic acid is greater than about 0.4% to about 0.9%, by weight,of the total composition of the present invention.
 8. The composition ofclaim 1, the total concentration of non-ionic and anionic polymer of thecompositions is from (or greater than) 0.4% (or about 0.4%) to about1.0% (or about 1.0%), by weight, of the total composition of the presentinvention.
 9. The composition of claim 1, wherein the surface tension ofthe composition ranges from about 40.8 dynes/cm to 51.9 dynes/cm asmeasured by the Rame-Hart—DROPimage Advanced Software Pendant DropMethod described in the specification.
 10. The composition of claim 1,wherein the rate of moisture loss for the composition is less than 1mg/3 minutes at 37° C. and 70% relative humidity as measured by the DVSIntrinsic Measurement System and DVS-Intrinsic Control Software Methoddescribed in the specification.
 11. The composition of claim 1, whereinthe composition has a viscosity of from about 30 to 100 cps at zeroshear as measured by the AR2000 Flow Test Method described in thespecification.
 12. The composition of claim 11, wherein the compositionshave a viscosity of less than 30 cps at the shear rate of blinking (1/100 sec.) as measured by the AR2000 Flow Test Method described in thespecification.
 13. The composition of claim 1, wherein the compositionhas an elastic modulus G′ greater than 0.70 (or about 0.70) Pascals anda phase angle δ of from about 40° to about 65° as measured by the BohlinCVOR Rheometer Visco-Elastic Property Test Method described in thespecification.
 14. The composition of claim 1, wherein the compositionhas: i. a surface tension ranging from about 40.8 dynes/cm to 51.9dynes/cm as measured by the Rame-Hart—DROPimage Advanced SoftwarePendant Drop Method described in the specification; ii. a rate ofmoisture loss of less than 1 mg/3 minutes at 37° C. and 70% relativehumidity as measured by the DVS Intrinsic Measurement System andDVS-Intrinsic Control Software Method described in the specification;iii. a viscosity of from about 30 to 100 cps at zero shear and aviscosity of less than 30 cps at the shear rate of blinking ( 1/100sec.) as measured by the AR2000 Flow Test Method described in thespecification; and iv. an elastic modulus G′ greater than 0.70 (or about0.70) Pascals and a phase angle δ of from about 40° to about 65° asmeasured by the Bohlin CVOR Rheometer Visco-Elastic Property Test Methoddescribed in the specification.